Probing chemical reactivity with the diphenyldiazomethane reaction

Abstract

Probing Chemical Reactivity with the Diphenyldiazomethane ReactionRates of organic reactions can be altered in a multitude of ways. The effects which cause rate changes have consequently lent themselves to widespread investigation, not only from an academic viewpoint, but also as an aid to industry and to medicine. An accelerated reaction will yield its products in less time, thereby reducing operating costs and freeing expensive equipment for other work. Alternatively, methods for stabilizing drugs are of constant concern to medicinal chemists, since compounds which undergo decomposition or unwanted side reactions are of little use in therapy.The physical-organic chemist, therefore, requires a suitable reaction system on which to study the effects of temperature, pressure, solvent, and other variables. One such system is the reaction between diphenyldiazomethane (DDM) and carboxylic acids-the "DDM reaction." As DDM becomes consumed in the reaction, its deep red color gradually disappears, and the resulting decrease in optical density is easily monitored speetrophotometrically. Thus, once the acid and DDM have been mixed in solution, the reaction can be followed without recourse to the sampling and subsequent product analyses of other kinetic techniques. Substituents introduced into the carboxylic acid often produce considerable variations in rate; a change of solvent may also have a similar effect. In addition, it is possible to work with very small amounts of materials. However, the fact that an acceptable mechanism exists for the DDM reaction in hydroxylic solvents probably overshadows all these advantages. It stands to reason that measurements made on a reaction without a full knowledge of that reaction run the risk of misinterpretation. Evaluation of kinetic data is difficult enough even in the absence of this extra hazard! The Diphenyldiazomethane Reaction A systematic investigation of the esterification of carboxylic acids by DDM was started by J. D. Roberts and his co-workers in 1949 (1-5). They followed the reaction of a number of acids with DDM in ethanol at 30°C and found that strong acids catalyzed the reaction between DDM and the solvent to give ethyl diphenylmethy] ether. Weak acids, however, gave the diphenylmethyl ester of the acid as the major product, along with the product of the acid-catalyzed reaction with the solvent. The reaction was found to be firstorder in both acid and DDM (3). As a result, it can be conveniently conducted under pseudo first-order condi-

Reaction of Diphenyldiazomethane with Benzoic Acids in Batch and Continuous Flow

“…The rates of reaction (pseudo-first-order and second-order) can thus be experimentally calculated. The batch study is of pedagogic value on its own merit as it provides in-depth understanding of electronic effect, solvent effects, and rate of reactions. , Benzoic acid, p -nitrobenzoic acid, and p -methylbenzoic acid were used as models in the studies conducted by the VIP teams and would be candidates of choice for batch study in instructional laboratories. In this second module, time may permit to setup and prepare the flow tubular reactor (constructed in the prior session or provided prebuilt) by cleaning it with anhydrous ethanol.…”